title: G-CSF suppresses allergic pulmonary inflammation, downmodulating cytokine, chemokine and eosinophil production.
abstract: OBJECTIVE
  Granulocyte Colony-Stimulating Factor (G-CSF), which mobilizes hemopoietic stem cells (HSC), is believed to protect HSC graft recipients from graft-versus-host disease by enhancing Th2 cytokine secretion. Accordingly, G-CSF should aggravate Th2-dependent allergic pulmonary inflammation and the associated eosinophilia. We evaluated the effects of G-CSF in a model of allergic pulmonary inflammation.
  
  
  METHODS
  Allergic pulmonary inflammation was induced by repeated aerosol allergen challenge in ovalbumin-sensitized C57BL/6J mice. The effects of allergen challenge and of G-CSF pretreatment were evaluated by monitoring: a) eosinophilia and cytokine/chemokine content of bronchoalveolar lavage fluid, pulmonary interstitium, and blood; b) changes in airway resistance; and c) changes in bone-marrow eosinophil production.
  
  
  RESULTS
  Contrary to expectations, G-CSF pretreatment neither induced nor enhanced allergic pulmonary inflammation. Instead, G-CSF: a) suppressed accumulation of infiltrating eosinophils in bronchoalveolar, peribronchial and perivascular spaces of challenged lungs; and b) prevented ovalbumin challenge-induced rises in airway resistance. G-CSF had multiple regulatory effects on cytokine and chemokine production: in bronchoalveolar lavage fluid, levels of IL-1 and IL-12 (p40), eotaxin and MIP-1a were decreased; in plasma, KC, a neutrophil chemoattractant, was increased, while IL-5 was decreased and eotaxin was unaffected. In bone-marrow, G-CSF: a) prevented the increase in bone-marrow eosinophil production induced by ovalbumin challenge of sensitized mice; and b) selectively stimulated neutrophil colony formation.
  
  
  CONCLUSIONS
  These observations challenge the view that G-CSF deviates cytokine production towards a Th2 profile in vivo, and suggest that this neutrophil-selective hemopoietin affects eosinophilic inflammation by a combination of effects on lung cytokine production and bone-marrow hemopoiesis.
authors.affiliation: Dept. of Pediatrics, Instituto Fernandes Figueira, FIOCRUZ, Rio de Janeiro, Brazil.
authors.forename: Túlio
authors.initials: T
authors.lastname: Queto
authors.forename: Zilton F M
authors.initials: ZF
authors.lastname: Vasconcelos
authors.forename: Ricardo Alves
authors.initials: RA
authors.lastname: Luz
authors.forename: Carina
authors.initials: C
authors.lastname: Anselmo
authors.forename: Ana Amélia A
authors.initials: AA
authors.lastname: Guiné
authors.forename: Patricia Machado R
authors.initials: PM
authors.lastname: e Silva
authors.forename: Júlia
authors.initials: J
authors.lastname: Farache
authors.forename: José Marcos T
authors.initials: JM
authors.lastname: Cunha
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Bonomo
authors.forename: Maria Ignez C
authors.initials: MI
authors.lastname: Gaspar-Elsas
authors.forename: Pedro
authors.initials: P
authors.lastname: Xavier-Elsas
mesh_terms: D000403:Airway Resistance / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002464:Cell Migration Inhibition / Q000276:immunology; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006131:Growth Inhibitors / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D018925:Chemokines; D016207:Cytokines; D006131:Growth Inhibitors; D016179:Granulocyte Colony-Stimulating Factor